Helicobacter pylori infection is strongly linked to gastric carcinoma. Only a small proportion of those infected develop gastric cancer. While host and environmental factors and genetic predisposition are likely to be important, the microorganism appears pivotal in "providing" the proper environment of atrophic pangastritis. For almost all bacterial pathogens studied to date, the majority of clinically significant disease outbreaks are caused by a very small percentage of the extant clones of a species. Recent large scale studies of genetic structure in natural populations of pathogenic bacteria revealed disease nature and severity were associated with specific clones of bacteria. The goal of this proposal is to clarify the role of Hp in gastric carcinoma by determining whether distinct Hp strains are more frequently associated with gastric cancer than duodenal ulcer, a disease with no association with gastric carcinoma. Putative genetic factors from these specific strains responsible for virulence will be identified and characterized. We will generate DNA fingerprints based on amplification of genomic regions between repetitive elements, a proven method for discriminating between strains within a species population. We intend to use the REP-PCR technique to generate genotypes for each strain obtained from gastric cancer patients and compare these with the fingerprints from strains obtained from first degree relatives and with strains from patients with non-malignant gastroduodenal disease such as simple gastritis and duodenal ulcer disease. Identification of disease-specific Hp cell lineages and their potential virulence factors will expand our knowledge of the mechanisms underlying the role of Hp in the pathogenesis of various gastrointestinal diseases and should lead to the development of more effective methods to investigate, treat, and prevent Hp-associated gastroduodenal disease.